Download pentose phosphate pathway

Pentose phosphate pathway
• Cells are provided with a constant supply of NADPH for
biosynthesis by the pentose phosphate pathway
• Also called the hexose monophosphate shunt
• This pathway also produces ribose-5-P to make RNA, DNA,
and coenzyme, ATP, NADH, FADH etc.
• This pathway consists of two oxidative processes followed by
five non-oxidative steps
• It operates mostly in the cytosol of liver and adipose cells
• NADPH is used in cytosol for fatty acid synthesis
Oxidative phase produce pentose phosphate and
NADPH
Nonoxidative phase recycles pentose phosphate to
G-6-P
1. Six five-carbon sugar phosphates are converted to five six-carbon sugar
phosphate.
2. Continued recycling leads ultimately to the conversion of glucose 6-phosphate
to six carbon dioxide
Transketolase
1. Catalyzes the transfer of a two-carbon fragment from a ketose donor to an
aldose acceptor.
Transaldolase
1. Catalyzes the transfer of a three-carbon fragment form a S-7-P to G-3-P for
forming F-6-P and E-4-P.
G-6-P is partitioned between glycolysis and the PPP
1. Entry of G-6-P either into glycolysis or into PPP is largely determined by the
relative concentrations of NADP+ and NADPH
2. NADP+ >NADPH, NADP+ allosterically stimulate G6PD, thereby increasing
the flux of G-6-P through the PPP
3. NADP+ <NADPH, PPP slows and G-6-P is used to fuel glycolysis
David L. Nelson and Michael M. Cox
LEHNINGER
PRINCIPLES OF BIOCHEMISTRY
Fifth Edition
CHAPTER 15
Principles of Metabolic Regulation
© 2008 W. H. Freeman and Company
Both the amount and the catalytic activity of an enzyme can be
regulated
1. Extracellular signal: hormonal, neuronal, growth factors etc.
2. Transcription: activate or repress the transcription
3. The stability of mRNA
4. The rate of translation
5. The rate of protein degradation
6. Sequester the enzyme and its substrate in different compartments
7. By the concentration of substrate
8. The presence of allosteric effector
9. Covalent modification
10. Binding of regulatory protein
Adenine Nucleotides play special Roles in Metabolic regulation
1.
2.
3.
4.
5.
It is important to maintain a constant supply and concentration of ATP: [ATP]
drop  reaction rate is decreased.
AMP concentration is more sensitive indicator of cell’s energetic state than is
[ATP]
AMP-activated protein kinase
- regulated by [AMP]
- A reduced nutrient supply or by increase exercise cause the rise in [AMP]
- increase glucose uptake, activates glycolysis and fatty acid oxidation
- suppress energy requiring processes such as fatty acid, cholesterol, and
protein synthesis
NADH and NADPH : change in their mass action ratios have global effects
on metabolism
Glucose
Coordinated Regulation of Glycolysis and Gluconeogensis
Hexokinase
1. Human have four isozyme, encoded by different genes
Isozyme: Different proteins that catalyze the same reaction
2. In myocytes, hexokinase II: high affinity for glucose, inhibited
by G-6-P
3. In liver, hexokinase IV (glucokinase)
- low affinity for glucose: direct regulation by the level of blood
glucose
- not inhibited by G-6-P
- is subjected to inhibition by reversible binding of a regulatory
protein specific to liver
- are transcriptionally regulated: [ATP] low or [glucose] high